title: Human umbilical cord mesenchymal stem cells inhibit C6 glioma growth via secretion of dickkopf-1 (DKK1).
abstract: Mesenchymal stem cells (MSCs) represent a potential therapeutic target for glioma. We determined the molecular mechanism of inhibitory effect of human umbilical cord-derived MSCs (hUC-MSCs) on the growth of C6 glioma cells. We demonstrated that hUC-MSCs inhibited C6 cell growth and modulated the cell cycle to G0/G1 phase. The expression of β-catenin and c-Myc was downregulated in C6 cells by conditioned media from hUC-MSCs, and the levels of secreted DKK1 were positively correlated with concentrations of hUCMSCs-CM. The inhibitory effect of hUC-MSCs on C6 cell proliferation was enhanced as the concentration of DKK1 in hUCMSCs-CM increased. When DKK1 was neutralized by anti-DKK1 antibody, the inhibitory effect of hUC-MSCs on C6 cells was attenuated. Furthermore, we found that conditioned media from hUC-MSCs transfection with siRNA targeting DKK1 mRNA or pEGFPN1-DKK1 plasmid lost or enhanced the abilities to regulate the Wnt signaling in C6 cells. Therefore, hUC-MSCs inhibited C6 glioma cell growth via secreting DKK1, an inhibitor of Wnt pathway, may represent a novel therapeutic strategy for malignant glioma.
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Ma
authors.forename: Shuo
authors.initials: S
authors.lastname: Liang
authors.forename: Hongliang
authors.initials: H
authors.lastname: Jiao
authors.forename: Liankai
authors.initials: L
authors.lastname: Chi
authors.forename: Xinyi
authors.initials: X
authors.lastname: Shi
authors.forename: Yi
authors.initials: Y
authors.lastname: Tian
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Fangxia
authors.initials: F
authors.lastname: Guan
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005910:Glioma / Q000473:pathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014470:Umbilical Cord / Q000166:cytology*; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D051176:beta Catenin